Magnetic particles are widely used reagents for the purification and extraction of nucleic acids. For example, U.S. Pat. Nos. 4,554,488 and 4,672,040 attach a nucleic acid to silanized magnetic particles that are about one micron in diameter. U.S. Pat. No. 5,898,071 utilizes one-micron silanized particles in the presence of polyethylene glycol (PEG) to extract DNA. Similar magnetic particles have been used to capture and release target nucleic acid for the detection of specific sequences of DNA (see, e.g., U.S. Pat. No. 5,750,338). Streptavidin has been attached to magnetic particles and can be used to recover biotinylated nucleic acids after sequence specific hybridization.
U.S. Pat. No. 5,512,439 describes attaching oligonucleotides to 1-10 micron microspheres impregnated with iron oxide and using the microspheres to bind to target nucleic acids, which can then be separated from their surrounding media.
U.S. Pat. No. 6,027,945 describes the use of magnetic silica particles having a diameter of 4-7 microns to extract and purify nucleic acids including DNA fragments, plasmid DNA, and RNA.
U.S. Pat. No. 5,508,164 describes linking chromosomes to silanized glass supports with disulfide crosslinking agents to link to cell organelles. Cell organelles are then labeled and biotinylated magnetic particles are used to magnetically recover the particles after separation from the solid support using reducing agents.
Preparations of magnetic particles designed for separation and extraction use particles that are amenable to easy manipulation by weak applied magnetic fields. These materials are typically micron sized and have a high magnetic moment per particle; their effects on water relaxation rate are unspecified and not relevant to their application. Nanoparticles do not respond to the weak, magnetic fields of hand held magnets.
Magnetic particles have also been used to assay for analytes based on their ability to bind analytes and change magnetic resonance (MR) relaxation rates. In U.S. Pat. No. 5,164,297, bovine serum albumin (BSA) coated magnetic particles were used to react with an antibody. Addition of BSA favors dissociation of the complex between the antibody and the BSA-coated iron oxide particles. As a result of this dissociation of aggregates, the solvent T2 relaxation time decreased (1/T2 increased) and the BSA concentration can be determined from T2.
In another example, WO 01/19405 describes the preparation and uses of magnetic nanoparticles with various biomacromolecules attached.